It is certain that under a variety of experimental conditions vasopressin will cause release of ACTH from the anterior pituitary, and high concentrations of vasopressin have been measured in the hypothalamic pituitary portal plexus. Furthermore, after adrenalectomy vasopressin accumulates in the median eminence in a position which would indicate increased secretion of vasopressin into the pituitary portal plexus. With the recent discovery of the structure of CRF, it is likely that further studies with administered CRF and administered vasopressin will be forthcoming which will show new ways in which vasopressin and CRF can interact at the level of the anterior pituitary. With all of this data the question remains whether vasopressin does act as a physiologic regulator of ACTH in the intact animal. To answer this question requires that the intrinsic secretion of vasopressin be perturbed in the intact animal and that the effect of these perturbations on the release of ACTH be examined. We bring to these studies two tools which have not been available for the study of these questions. We will block the action of released vasopressin in the intact animal by administration of antibody which specifically binds vasopressin or by administration of an analogue which competes at the receptor site to block the action of vasopressin to stimulate the release of ACTH. During the administration of these agents, the release of ACTH (and corticosterone) will be examined in adrenallectomized rats and in rats subjected to a variety of stresses which release ACTH through neural pathways. The specificity of positive results will be checked by repeat studies in the Brattleboro rat and some studies with administered CRF will be raised and further studies are outlined in which the relative contribution of CRF and vasopressin to the release of ACTH during stress will be measured. We are one of the few labs in the world which has sufficient antivasopressin antibody to undertake these studies and the results will be of great interest scientificially to determine whether vasopressin is a physiologic regulator of ACTH release.